Sign up to receive free email alerts when patent applications with chosen keywords are publishedSIGN UP

Abstract:

Provided is a nerve stimulation apparatus that is capable of performing
effective nerve stimulation depending on a therapeutic purpose without
adversely affecting a heart. Further provided is a nerve stimulation
apparatus including: a stimulation-pulse output unit that outputs a
stimulation pulse; a cardiac-event detector that detects a cardiac event;
and a controller that controls the stimulation-signal output unit so as
to output, during a cardiac refractory period, the nerve stimulation
signal having an intensity that corresponds to the heart rate obtained on
the basis of the cardiac event detected by the cardiac-event detector.

Claims:

1. A nerve stimulation apparatus comprising: a stimulation-signal output
unit that outputs a nerve stimulation signal; a cardiac-event detector
that detects a cardiac event; and a controller that controls the
stimulation-signal output unit so as to output, during a cardiac
refractory period, the nerve stimulation signal having an intensity that
corresponds to a heart rate obtained on the basis of the cardiac event
detected by the cardiac-event detector.

2. A nerve stimulation apparatus according to claim 1, wherein the
controller changes at least one of a pulse voltage, a pulse duration, a
number of pulses, and a pulse period of the pulsed nerve stimulation
signal output from the stimulation-signal output unit.

3. A nerve stimulation apparatus according to claim 2, wherein the
controller changes the number of pulses and the pulse period of the nerve
stimulation signal output from the stimulation-signal output unit under a
condition such that the product of the number of pulses and the pulse
period of the nerve stimulation signal is equal to or less than a
predetermined value.

4. A nerve stimulation apparatus according to claim 1, wherein the nerve
stimulation signal is transmitted to a vagus nerve, and the controller
changes an intensity of the nerve stimulation signal output from the
stimulation-signal output unit in proportion to the heart rate that is
obtained on the basis of the cardiac event detected by the cardiac-event
detector.

5. A nerve stimulation apparatus according to claim 1, wherein the nerve
stimulation signal is transmitted to a vagus nerve, and the controller
changes a rate of change of intensity of the nerve stimulation signal
output from the stimulation-signal output unit according to the heart
rate that is obtained on the basis of the cardiac event detected by the
cardiac-event detector.

6. A nerve stimulation apparatus according to claim 1, wherein the nerve
stimulation signal is transmitted to a vagus nerve, and the controller
controls the stimulation-signal output unit so as to keep an intensity of
the nerve stimulation signal constant in relation to the heart rate
obtained on the basis of the cardiac event detected by the cardiac-event
detector.

7. A nerve stimulation apparatus according to claim 1, wherein the nerve
stimulation signal is transmitted to a sympathetic nerve, and the
controller changes an intensity of the nerve stimulation signal output
from the stimulation-signal output unit in inverse proportion to the
heart rate obtained on the basis of the cardiac event detected by the
cardiac-event detector.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is based on Japanese Patent Application No.
2011-201949, the contents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to a nerve stimulation apparatus.

[0004] 2. Description of Related Art

[0005] Stimulation of the vagus nerve on a patient who has experienced
cardiac infarction has conventionally known to be capable of suppressing
cardiac remodeling (for example, see WO2006/098996). In addition, it has
been proposed that stimulation of the vagus nerve over a long period of
time on a patient experiencing cardiac failure can potentially prevent
progress of the disease.

[0006] In the related art described above, in order to perform cardiac
treatment on a patient, remodeling control therapy is performed by
biventricular pacing, and anti-remodeling therapy is performed by nerve
stimulation. In addition, by performing nerve stimulation in the cardiac
refractory period, undesired stimulation of the heart due to leakage of
nerve stimulation is prevented so that the heart is not adversely
affected.

BRIEF SUMMARY OF THE INVENTION

[0007] The present invention provides a nerve stimulation apparatus that
is capable of performing effective nerve stimulation depending on the
therapeutic purpose while preventing the heart from being adversely
affected.

[0008] The present invention employs following solution.

[0009] An aspect of according to the present invention is a nerve
stimulation apparatus including: a stimulation-signal output unit that
outputs a nerve stimulation signal; a cardiac-event detector that detects
a cardiac event; and a controller that controls the stimulation-signal
output unit so as to output, during a cardiac refractory period, the
nerve stimulation signal having an intensity that corresponds to the
heart rate obtained on the basis of the cardiac event detected by the
cardiac-event detector.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0010] FIG. 1 is a diagram showing the overall configuration of a nerve
stimulation apparatus according to an embodiment of the present
invention.

[0011] FIG. 2 is a flowchart showing a procedure for the nerve stimulation
apparatus of FIG. 1.

[0012]FIG. 3 is a time chart showing the relationship between an
electrocardiac signal and a stimulation intensity of the nerve
stimulation apparatus of FIG. 1.

[0014] FIG. 5 is a table showing examples of parameter settings in a
proportional mode.

[0015]FIG. 6 is a graph showing the relationship between the heart rate
and the relative intensity of stimulation pulses in the proportional
mode.

[0016] FIG. 7 is a table showing examples of parameter settings in a
variable rate-of-change-of-intensity mode.

[0017] FIG. 8 is a graph showing the relationship between the heart rate
and the relative intensity of stimulation pulses in the variable
rate-of-change-of-intensity mode.

[0018] FIG. 9 is a table showing examples of parameter settings in a
nonvariable mode.

[0019]FIG. 10 is a graph showing the relationship between the heart rate
and the relative intensity of stimulation pulses in the nonvariable mode.

[0020] FIG. 11 is a table showing examples of parameter settings in an
inversely proportional mode.

[0021]FIG. 12 is a graph showing the relationship between the heart rate
and the relative intensity of stimulation pulses in the inversely
proportional mode.

DETAILED DESCRIPTION OF THE INVENTION

[0022] The nerve stimulation apparatus 1 according to an embodiment of the
present invention will be described below, with reference to the
drawings.

[0023] As shown in FIG. 1, the nerve stimulation apparatus 1 according to
this embodiment is provided with electrodes 2 attached to a nerve N in
the vicinity of a heart H, such as the vagus nerve etc., a cardiac-event
detector 3 that detects an event in the heart H (cardiac event), a
stimulation-pulse output unit (stimulation-signal output unit) 4 that
outputs a stimulation pulse (nerve stimulation signal) to the nerve N
through the electrodes 2, and a controller 5 that controls the
stimulation-pulse output unit 4 on the basis of the cardiac event
detected by the cardiac-event detector 3.

[0024] The cardiac-event detector 3 is provided with two or more
indwelling detection electrodes 6 that are in contact with parts of the
heart H (for instance, in the example shown in FIG. 1, the right atrium
RA and the right ventricle RV), a signal detector 7 that detects an
electrocardiac signal though the two or more detection electrodes 6, and
a depolarization determination unit 8 that determines that, when the
signal detected with the signal detector 7 exceeds a predetermined
threshold, the heart H is undergoing depolarization at that point. In the
figure, reference sign LA is the left atrium, and reference sign LV is
the left ventricle.

[0025] In the example shown in FIG. 1, the detection electrodes 6 are
placed in the right atrium RA and the right ventricle RV; however,
depolarization may be determined by using either an electrocardiac signal
of the right atrium RA or an electrocardiac signal of the right ventricle
RV, or both.

[0026] In addition, the locations where the detection electrodes 6 are
placed are not limited to the right atrium RA and the right ventricle RV:
for example, the left atrium LA and the left ventricle LV may be used.

[0027] The respective detection electrodes 6 consist of a cathode (tip
electrode) and an anode (ring electrode), and the respective electrodes
are connected to conductive wires. The conductive wires are coated with
an insulator so as not to cause a short circuit between the cathode and
the anode. These insulator-coated wires are further coated with an
insulator after the two wires are bound together (in the figure, the
insulating coating is omitted). The signal detector 7 detects an electric
potential difference formed between the cathode and the anode of the
respective detection electrodes 6 as an electrocardiac signal.

[0028] The stimulation-pulse output unit 4 generates a stimulation pulse
train for electrically stimulating the nerve N and supplies the nerve N
with the generated stimulation pulse train via the electrodes 2.
Parameters that determine the intensity of the stimulation pulse train
include pulse voltage, pulse duration, number of pulses, and pulse period
(frequency). A group of these parameters is called a burst, and the
number of pulses in one burst is called the number of pulses. In
addition, the interval between the bursts is called a burst period.

[0029] The electrodes 2 also consist of a cathode (tip electrode) and an
anode (ring electrode), and the respective electrodes are connected to
conductive wires. The conductive wires are coated with an insulator so as
not to cause a short circuit between the cathode and the anode. These
insulator-coated wires are further coated with an insulator after the two
wires are bound together (in the figure, the insulator coating is
omitted). The stimulation-pulse output unit 4 outputs the stimulation
pulse train, which is to be supplied to the nerve N, between the cathode
and the anode of the electrodes 2.

[0030] When the depolarization determination unit 8 determines that
depolarization of the heart H has occurred, it outputs to the controller
5 a signal indicating that the depolarization has occurred.

[0031] The controller 5 is provided with a timer (not shown). The
controller 5 resets the timer and starts measuring the elapsed time every
time the signal indicating the occurrence of depolarization is received
from the depolarization determination unit 8.

[0032] A refractory period of the heart H of 150 ms, for example, is
stored and held in the controller 5 as a predetermined value, and the
period of 150 ms from the time at which the signal indicating the
occurrence of depolarization is received from the depolarization
determination unit 8 is determined as the refractory period. In addition,
the controller 5 controls the stimulation-pulse output unit 4 so as to
output, during cardiac refractory periods, stimulation pulses having an
intensity that corresponds to the heart rate obtained on the basis of the
cardiac event detected by the cardiac-event detector 3. The value of this
refractory period is stored and held in the controller 5 by inputting to
the controller 5, in advance, an actually measured value of the duration
of the refractory period of a patient or a general value.

[0033] In particular, the controller 5 changes at least one of the pulse
voltage, the pulse duration, the number of pulses, and the pulse period
of the stimulation pulse output from the stimulation-pulse output unit 4
in accordance with the selected stimulation mode. The intensity of the
stimulation pulse per burst can be defined by three parameters, i.e. the
pulse voltage, the pulse duration, and the number of pulses, and in
addition, a stimulation intensity per unit time can be defined by taking
a parameter of the burst period into account. In this embodiment, the
burst periods are matched with the depolarization intervals. Therefore,
the controller 5 can change the intensity of the nerve stimulation signal
output from the stimulation-pulse output unit 4 by changing at least one
of the pulse voltage, the pulse duration, and the number of pulses.

[0034] The stimulation mode includes a proportional mode in which the
stimulation pulse intensity is proportional to the heart rate, a variable
rate-of-change-of-intensity mode in which the rate of change of the
stimulation pulse intensity is changed according to the heart rate, a
nonvariable mode in which the stimulation pulse intensity is maintained
constant, and an inversely proportional mode in which the stimulation
pulse intensity is inversely proportional to the heart rate. Details of
these stimulation modes will be described later.

[0035] A procedure for the nerve stimulation apparatus 1 according to this
embodiment, having the configuration described above, will be described
below according to the flowchart in FIG. 2.

[0036] In the nerve stimulation apparatus 1 according to this embodiment,
selection of the aforementioned stimulation mode (the proportional mode
M1, the variable rate-of-change-of-intensity mode M2, the nonvariable
mode M3, and the inversely proportional mode M4) is performed (Step S1).
At this time, the selection of the stimulation mode may be performed by
pushing a switch (not shown) etc. provided on the nerve stimulation
apparatus 1 or by being programmed by a user.

[0037] Next, reference stimulation parameters for the stimulation pulse
intensity and the amounts of change of the parameters are set (Step S2).
The setting may be performed by a user through an external program or by
utilizing values preset in a memory (not shown) of the nerve stimulation
apparatus 1.

[0038] Next, an electrocardiac signal formed across the detection
electrodes 6 of the cardiac-event detector 3 that indwell in the heart H
is detected with the signal detector 7, the occurrence of depolarization
of the heart H is determined by the depolarization determination unit 8
when the detected electrocardiac signal exceeds a predetermined
threshold, and a signal indicating so is sent to the controller 5.

[0039] As the signal indicating that the depolarization has occurred is
sent to the controller 5, the controller 5 resets the timer to start the
timer for measuring depolarization intervals (Step S3).

[0040] Thereafter, the controller 5 stands-by until it receives a
depolarization notification from the depolarization determination unit 8
while keep measuring the elapsed time with the timer (Step S4).

[0041] The controller 5 calculates a depolarization interval every time it
receives a depolarization notification from the depolarization
determination unit 8 and resets the timer (restarts) (Step S5).

[0042] Thereafter, on the basis of the depolarization interval (the
instantaneous heart rate) and the reference stimulation parameters, the
controller 5 decides stimulation parameters and notifies the
stimulation-pulse output unit 4 of the stimulation parameters (Step S6).

[0043] Unless a termination notification is received from a user or a
program, the aforementioned Steps S4 to S6 are repeated.

[0044] Next, an operation example of the nerve stimulation apparatus 1
according to this embodiment will be described below with reference to
the time charts of FIG. 3.

[0045] In FIG. 3, the top section shows the electrical activity of the
heart detected with the signal detector 7 and timings (parts indicated as
"depolarization" in the figure) at which depolarizations are determined
with the depolarization determination unit 8.

[0046] In FIG. 3, the middle section shows the depolarization intervals
(800 ms, 600 ms, and 1000 ms) and duration of the cardiac refractory
period measured by the controller 5 using the timer. In the figure,
numerical values in parentheses (75 bpm, 100 bpm, and 60 bpm) indicate
the instantaneous heart rate, and the cardiac refractory period is for
example, 150 ms.

[0047] The bottom section in FIG. 3 shows a situation in which the
stimulation-pulse output unit 4, which has been notified of the
stimulation parameters from the controller 5, is outputting the
stimulation pulses during the cardiac refractory periods. The vertical
axis indicates the nerve stimulation voltage, in particular, voltages of
the stimulation pulses, and the voltages are, for example, 4 V, 3 V, and
5 V.

[0048] The depolarization intervals and the heart rate will now be
explained.

[0049] As shown in the following equation, the heart rate (unit: bpm)
normally means the number of heartbeats (=the number of depolarizations)
per minute; however, a depolarization interval converted to heart rate
can also be called the heart rate (strictly, the instantaneous heart
rate).

[0050] In addition, an example of the stimulation pulses is shown in FIG.
4.

[0051] The parameters notified to the stimulation-pulse output unit 4 from
the controller 5 include the pulse voltage, the pulse duration, the pulse
period, and the number of pulses. As mentioned above, the intensity of
the stimulation pulse per burst can be defined by three parameters, i.e.,
the pulse voltage, the pulse duration, and the number of pulses. Each of
the parameters may be changed independently to change the intensity, or
two or more parameters may be changed in combination to change the
intensity.

[0052] As described above, according to the nerve stimulation apparatus 1
of this embodiment, the cardiac-event detector 3 detects the cardiac
event, and the heart rate is obtained on the basis of the cardiac event.
The controller 5 then controls the stimulation-pulse output unit 4 so as
to output, during the cardiac refractory period, a stimulation pulse
having an intensity corresponding to the heart rate.

[0053] By performing nerve stimulation during the cardiac refractory
period in such a manner, it is possible to prevent undesired stimulation
of the heart due to leakage of nerve stimulation and to prevent the heart
from being adversely affected. In addition, by changing the stimulation
pulse intensity according to the heart rate, it is possible to
effectively perform nerve stimulation regardless of variations of the
depolarization intervals. In other words, with the nerve stimulation
apparatus 1 of this embodiment, it is possible to effectively perform
nerve stimulation without adversely affecting the heart.

[0054] Methods of deciding stimulation parameters in the respective
stimulation modes (i.e., the proportional mode, the variable
rate-of-change-of-intensity mode, the nonvariable mode, and the inversely
proportional mode) mentioned above using the nerve stimulation apparatus
1 according to this embodiment will be described below for each
stimulation mode.

<Proportional Mode>

[0055] The proportional mode is a stimulation mode in which the
stimulation intensity per unit time is proportional to the heart rate.

[0056] Reduction of the heart rate, prevention of lethal arrhythmia, and a
therapeutic effect on cardiac failure can be expected as results of
stimulation of the vagus nerve; however, in particular, tachycardia
therapy (reduction of the heart rate and prevention of lethal arrhythmia)
is the aim of this stimulation mode.

[0057] Examples of stimulation parameters in this stimulation mode are
shown in FIG. 5.

[0058] As shown in FIG. 5, in this stimulation mode, the respective
stimulation parameters are set such that the stimulation intensity per
unit time is proportional to the heart rate. As mentioned above, the
stimulation parameters include the pulse voltage, the pulse duration, the
number of pulses, and the pulse period. The stimulation intensity per
unit time (relative value) is defined by the product of the heart rate,
the pulse voltage, the pulse duration, and the number of pulses. In
addition, the product of the number of pulses and the pulse period
defines a pulse output period, and it needs to be shorter than the
cardiac refractory period (in this example, 150 ms).

[0059] In FIG. 5, in the case where the stimulation intensity (5000) for
the heart rate of 100 bpm (the pulse voltage: 5.0 V, the pulse duration:
2 ms, the number of pulses: five times, and the pulse period: 20 ms) is
set as a reference, the relative intensity means the magnitude of the
stimulation intensity for the respective heart rates relative to the
reference.

[0060] As described above, when the proportional mode is set using the
nerve stimulation apparatus 1 according to this embodiment, the
stimulation pulses are transmitted to the vagus nerve, and the controller
5 causes the intensity of the stimulation pulses output from the
stimulation-pulse output unit 4 to be changed in proportion to the heart
rate obtained on the basis of the cardiac event detected by the
cardiac-event detector 3.

[0061] By doing so, regardless of the durations of the depolarization
intervals, as shown in FIG. 6, it is possible to stimulate the vagus
nerve by changing the intensity of the stimulation pulse per unit time in
proportion to the heart rate and to perform an effective tachycardia
therapy.

<Variable Rate-of-Change-of-Intensity Mode>

[0062] The variable rate-of-change-of-intensity mode is a stimulation mode
in which the rate of change of the stimulation intensity per unit time is
changed according to the heart rate.

[0063] Although a simple proportional relationship is involved in the
aforementioned proportional mode, the variable
rate-of-change-of-intensity mode can further increase the intensity when
the heart rate is high.

[0064] Examples of stimulation parameters in this stimulation mode are
shown in FIG. 7.

[0065] As shown in FIG. 7, in this stimulation mode, the respective
stimulation parameters are set such that the rate of change of the
stimulation intensity per unit time is changed in accordance with the
heart rate.

[0066] In this stimulation mode, the reference stimulation parameters are
the same as the respective parameter values (pulse voltage: 5.0 V, pulse
duration: 2 ms, number of pulses: 5, and pulse period: 20 ms) when the
heart rate is 100 bpm. In addition, the amounts of change in the
parameters are set as follows: pulse voltage: 0.5 V, pulse duration: 0.2
ms, number of pulses: 1, and pulse period: 1 ms.

[0067] As divisions for changing the stimulation parameters, analysis is
possible by dividing the parameters into four regions A to D.

[0068] In the region A, the stimulation intensity per unit time is
adjusted by changing the pulse voltage. In this example, the variable
range of the pulse voltage is set from 3.0 V to 7.0 V.

[0069] In the region B, the stimulation intensity per unit time is
adjusted by changing the pulse duration. In this example, the variable
range of the pulse duration is set from 1 ms to 3 ms. At this time, the
pulse voltage is the upper limit or the lower limit.

[0070] In the region C, the stimulation intensity per unit time is
adjusted by changing the number of pulses. At this time, the pulse
voltage and the pulse duration are the upper limits or the lower limits.

[0071] In the region D, the stimulation intensity per unit time is
adjusted by changing the number of pulses and the pulse period. At this
time, adjustment is made such that the product of the number of pulses
and the pulse period does not exceed the cardiac refractory period (in
this example, 150 ms).

[0072] As described above, when the variable rate-of-change-of-intensity
mode is set using the nerve stimulation apparatus 1 according to this
embodiment, the stimulation pulses are transmitted to the vagus nerve,
and the controller 5 causes the rate of change of the intensity of the
stimulation pulses output from the stimulation-pulse output unit 4 to be
changed according to the heart rate obtained on the basis of the cardiac
event detected by the cardiac-event detector 3.

[0073] By doing so, regardless of the durations of the depolarization
intervals, as shown in FIG. 8, it is possible to stimulate the vagus
nerve by changing the rate of change of the stimulation pulse intensity
according to the heart rate to change the stimulation pulse intensity,
and in particular, it is possible to perform an effective tachycardia
therapy when the heart rate is high.

<Nonvariable Mode>

[0074] The nonvariable mode is a mode in which the stimulation intensity
per unit time is constant regardless of the heart rate.

[0075] In this stimulation mode, the aim is to treat cardiac failure with
stimulation of the vagus nerve. With this stimulation mode, it is
possible to constantly provide a patient with stimulation at a level
decided by a doctor without being affected by fluctuation of the
heartbeat.

[0076] Examples of stimulation parameters in this stimulation mode are
shown in FIG. 9.

[0077] As shown in FIG. 9, in this stimulation mode, the respective
stimulation parameters are set such that the stimulation intensity per
unit time is kept constant regardless of the heart rate.

[0078] In this stimulation mode, the reference stimulation parameters are
the same as the respective parameter values (pulse voltage: 5.0 V, pulse
duration: 2 ms, number of pulses: 5, and pulse period: 20 ms) when the
heart rate is 100 bpm. In addition, the amounts of change in parameters
are set as followings: pulse voltage: 0.1 V, pulse duration: 0.2 ms,
number of pulses: 1, and pulse period: 1 ms.

[0079] As divisions for changing the stimulation parameters, similarly to
the variable rate-of-change-of-intensity mode (see FIG. 7), analysis is
possible by dividing the parameters into four regions A to D.

[0080] In the region A, the stimulation intensity per unit time is
adjusted to be constant by changing the pulse voltage. In this example,
the variable range of the pulse voltage is set from 3.0 V to 7.0 V.

[0081] In the region B, the stimulation intensity per unit time is
adjusted to be a constant by changing the pulse duration. In this
example, the variable range of the pulse duration is set to 1 ms to 3 ms.
At this time, the pulse voltage is the upper limit or the lower limit.

[0082] In the region C, the stimulation intensity per unit time is
adjusted so as to become constant by changing the number of pulses. At
this time, the pulse voltage and the pulse duration are the upper limits
or the lower limits.

[0083] In the region D, the stimulation intensity per unit time is
adjusted so to become constant by changing the number of pulses and the
pulse period. At this time, adjustment is made such that the product of
the number of pulses and the pulse period do not exceed the cardiac
refractory period (in this example, 150 ms).

[0084] As described above, when the nonvariable mode is set using the
nerve stimulation apparatus 1 according to this embodiment, the
stimulation pulses are transmitted to the vagus nerve, and the controller
5 controls the stimulation-pulse output unit 4 such that the stimulation
pulse intensity becomes constant according to the heart rate obtained on
the basis of the cardiac event detected by the cardiac-event detector 3.

[0085] By doing so, regardless of the duration of the depolarization
intervals, as shown in FIG. 10, it is possible to stimulate the vagus
nerve while keeping the stimulation pulse intensity constant and to
perform effective therapy for cardiac failure.

<Inversely Proportional Mode>

[0086] The inversely proportional mode is a stimulation mode in which the
stimulation intensity per unit time is inversely proportional to the
heart rate.

[0087] In this stimulation mode, the heart rate can be increased by
stimulating the sympathetic nerve, and therefore, this mode can be
applied to bradycardia therapy.

[0088] Examples of stimulation parameters in this stimulation mode are
shown in FIG. 11.

[0089] As shown in FIG. 11, in this stimulation mode, the respective
stimulation parameters are set such that the stimulation intensity per
unit time is inversely proportional to the heart rate.

[0090] In this stimulation mode, the reference stimulation parameters are
the same as the respective parameter values (pulse voltage: 5.0 V, pulse
duration: 2 ms, number of pulses: 5, and pulse period: 20 ms) when the
heart rate is 60 bpm. In addition, the amounts of change in parameters
are set as followings: pulse voltage: 0.5 V, pulse duration: 0.2 ms,
number of pulses: 1, and pulse period: 1 ms.

[0091] As divisions for changing the stimulation parameters, similarly to
the variable rate-of-change-of-intensity mode (see FIG. 7), analysis is
possible by dividing the parameters into four regions A to D.

[0092] In the region A, the stimulation intensity per unit time is
adjusted by changing the pulse voltage. In this example, the variable
range of the pulse voltage is set from 3.0 V to 7.0 V.

[0093] In the region B, the stimulation intensity per unit time is
adjusted by changing the pulse duration. In this example, the variable
range of the pulse duration is set to 1 ms to 3 ms. At this time, the
pulse voltage is the upper limit or the lower limit.

[0094] In the region C, the stimulation intensity per unit time is
adjusted by changing the number of pulses. At this time, the pulse
voltage and the pulse duration are the upper limits or the lower limits.

[0095] In the region D, the stimulation intensity per unit time is
adjusted by changing the number of pulses and the pulse period. At this
time, adjustment is performed such that the product of the number of
pulses and the pulse period does not exceed the cardiac refractory
period.

[0096] As described above, when the inversely proportional mode is set
using the nerve stimulation apparatus 1 according to this embodiment, the
stimulation pulses are transmitted to the sympathetic nerve, and the
controller 5 causes the intensity of the stimulation pulses output from
the stimulation-pulse output unit 4 to be changed in inverse proportion
to the heart rate obtained on the basis of the cardiac event detected by
the cardiac-event detector 3.

[0097] By doing so, regardless of the durations of the depolarization
intervals, as shown in FIG. 12, it is possible to stimulate the
sympathetic nerve by changing the stimulation pulse intensity in inverse
proportion to the heart rate and to perform effective bradycardia
therapy.

[0098] Although an embodiment of the present invention has been described
above in detail with reference to the drawings, the specific
configurations are not limited to this embodiment, and design alterations
and the like within a range that does not depart from the spirit of the
present invention are encompassed.

[0099] For example, the heart rate is exemplified by the instantaneous
heart rate obtained from two depolarizations; however, the controller 5
may hold depolarization intervals for several depolarizations and
calculate the average thereof. By doing so, it is possible to suppress
sudden change in the stimulation parameters.

[0100] In addition, in each of the stimulation modes, all of the
parameters, i.e., the pulse voltage, the pulse duration, the number of
pulses, and the pulse period are changed; however, just some of the
parameters may be unchanged.

[0101] In addition, in this embodiment, a predetermined value is stored in
the controller 5 and the apparatus is controlled by performing
determinations on the basis of the predetermined value; however, the
nerve stimulation apparatus may be provided with a storage unit, and
values may be stored in the storage unit.